No. 1, January 2005
The Vital Link Between
Chronic Disease and Depressive Disorders
Daniel P. Chapman, PhD, Geraldine S. Perry, DrPH, Tara W.
Suggested citation for this article: Chapman DP, Perry
GS, Strine TW. The vital link between chronic disease and depressive disorders. Prev
Chronic Dis [serial online] 2005 Jan
[date cited]. Available from: URL:
Chronic diseases have assumed an increasingly important role in public health research and intervention.
Without treatment, depressive disorders characteristically assume a
chronic course and are expected, by 2020, to be second only to heart disease in the
global burden of disease. Thus, understanding the
relationship between depressive disorders and chronic disease appears vital
to public health assessment and health care delivery.
Articles for review were primarily identified by a Medline search
emphasizing the subject headings mental disorders or depression
crossed with selected chronic diseases and conditions including
asthma, arthritis, cardiovascular disease, cancer, diabetes, and
Mental illnesses — most specifically, depressive
disorders — were associated with increased prevalence of chronic
diseases. This association between depression and chronic disease appears attributable to depressive
disorders precipitating chronic disease and to chronic disease
exacerbating symptoms of depression. The complex interrelationship between
depressive disorders and chronic disease has important implications for
both chronic disease management and the treatment of depression.
Depressive disorders assume an important role in the
etiology, course, and outcomes associated with chronic disease.
Multivariate community-based research and intervention fostering the
detection and treatment of depressive disorders is needed, as is further
examination of the role exerted by mental illnesses other than depression in
the pathogenesis of chronic disease.
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Recent research indicates that seven out of 10 office visits
to a primary care practitioner concern chronic diseases (1). As the management of chronic
diseases has assumed an increasingly vital role in health care
delivery, recognition of the importance of depressive disorders
has also grown. By 2020, depression is expected to be second only to heart
disease as a source of the global burden of disease (2). As chronic disease and depressive disorders are
increasingly recognized as major impediments to health,
understanding the connection between them becomes of utmost
importance to providing quality health care.
Despite the growing recognition of the importance of both
chronic disease and depressive disorders to the health of
individuals and communities, research examining their
interrelationship has been the subject of surprisingly little
empirical review. A Medline search for literature reviews
emphasizing both chronic disease and depression yielded only two
publications. These articles addressed factors germane to
health-service costs (3) and individual characteristics
precipitating the onset of depressive disorders subsequent to the
development of chronic disease (4). While raising important
concerns, previous reviews were deliberately limited in scope and
did not generally address disease-specific variables potentially
underlying the associations between depressive disorders and a
number of chronic diseases. To better address this issue, we
reviewed the research literature examining the relationships
between depressive disorders and prevalent chronic diseases that
are also of programmatic relevance to the work of the Centers for
Disease Control and Prevention.
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Articles included in this review were primarily identified through
a Medline search of the terms mental disorders or depression crossed
with the chronic diseases and conditions asthma,
arthritis, cardiovascular disease, cancer, diabetes,
and obesity. These chronic diseases were selected because
they have been identified as highly prevalent and as major
sources of morbidity and mortality among U.S. adults. Studies
included for review were generally limited to empirical
investigations that provided definitional or diagnostic criteria
for both depression and relevant chronic diseases and that
featured a specified time course.
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Nearly 50% of asthma patients may suffer from clinically
significant depressive symptoms (5), which have been, in part, attributed to the stress of having a chronic illness (6). In
particular, persons with asthma who experience disruptive
symptoms, such as dyspnea and nighttime awakening, are at
increased risk for major depression (7). The presence of
depression among persons with asthma assumes particular gravity
because increased depressive symptoms have been associated with
poorer asthma outcomes (8), such as impaired voluntary activation
of the diaphragm (9). In clinical samples of children and
adolescents, asthma has been associated with the presence of an
anxiety disorder (10) and with anxious depressive symptoms among
youth with moderate and severe persistent asthma (11).
It appears that the symptoms — rather than the diagnosis
— of asthma are associated with depression or anxiety (12):
87.5% of persons with frequent asthma attacks manifest
psychopathology, compared with 25% of persons with less frequent
attacks (13). Similarly, among persons whose asthma is difficult
to control, psychopathology — primarily anxiety and
depressive symptoms — was associated with more frequent
visits to primary care providers and emergency departments and with more hospitalizations (14). Psychological morbidity
is associated with poor adherence to medication regimens (15),
and mothers of children with asthma are at risk for increased
depressive symptoms (16). Early assessment and intervention
addressing depressive disorders improves treatment adherence and
outcomes and may also decrease mortality (17).
Cognitive behavioral therapy (CBT) — in which the
individual is instructed to monitor and challenge self-negating
thoughts — has yielded a significant decrease in asthma
symptoms and depression (18). Likewise, physical
inactivity has been speculated to augment the strength of the
association between perceived stressors and depression in persons
with asthma, suggesting that exercise may ameliorate this association
and decrease the likelihood of depression in this population
Depression and/or anxiety are among the most commonly reported
concerns by persons with arthritis (20). Screening of patients
with arthritis revealed that depression was associated with activity
restriction, further suggesting that nonpsychiatric physicians should be
aware of the mental health status of patients with chronic
illnesses (21). Persons with arthritis experiencing
arthritis-based disability (22) and the recurrence of arthritic
symptoms (23) reported greater depression. Research on
adolescents and young adults with arthritis has found that
functional status is significantly correlated with depression, self-esteem, and
loneliness (24); significantly greater
depression was reported among those experiencing more severe
Research on the Arthritis Self-Management Program found that
participation in this intervention had a positive effect on
perceptions of self-efficacy, communication with
physicians, fatigue, anxiety, pain, and depression (25). A randomized
trial of an intervention designed to improve mood (antidepressant
medications and/or six to eight sessions of psychotherapy)
improved depression and fostered improvements in functional
status and quality of life (26). CBT has proven particularly effective in
ameliorating depressive symptoms when initiated early in the course of
rheumatoid arthritis (27) and when tailored to the concerns reported by persons
with rheumatoid arthritis, such as fatigue or mood (28). Similarly,
antidepressant medication has been associated with significant
improvements in both psychological status and health status in
persons with rheumatoid arthritis (29).
Rest and inactivity were previously considered to be reasonable therapeutic approaches in the management of
osteoarthritis until it was recognized that physical inactivity
contributed to disability and impaired functioning. Subsequent
research suggests that a tailored program of aerobic or
resistance-based exercise may be an important component of
self-managing osteoarthritis (30). Aerobic exercise has been
found to both ameliorate depressive symptoms and to reduce
disability and pain among persons with arthritis (31).
Depressive disorders have been associated with risk factors
for cardiovascular disease (CVD), such as smoking and
physical inactivity (32), and mental illness, in general, has been associated
with increased mortality due
to CVD (33). In general, persons who are depressed are much more
likely to develop coronary artery disease (34), and meta-analyses reveal
that the relative risk for developing heart disease in
individuals with depression or depressive symptoms is approximately 1.6 times greater
than among nondepressed persons (35,36), which is more than the
risk conferred by passive smoking (36). A stronger effect size
was reported for clinical depression than for depressive
symptoms, suggesting the presence of a dose-response relationship
(35). Depression has been positively associated with the
metabolic syndrome among women (but not men) younger than 40
years (37), suggesting that early detection and treatment of depression
may potentially forestall the risk of cardiovascular disease
Depression or depressive symptoms are also predictive of
stroke (38): persons with significant depressive symptoms are
approximately twice as likely as those with few depressive symptoms to have
a stroke within 10 years (39). Moreover, depression is associated
with an increased risk for stroke morbidity and mortality
In addition to being a predictor of stroke, depression commonly develops
after a stroke, especially after a stroke affecting the
left hemisphere of the brain (41). More than half of patients
experiencing a stroke report depressive symptoms within 18 months
of having a stroke (42). Post-stroke depression has been
associated with impairments in response to rehabilitation (43)
and with increased mortality up to two years following the stroke
(44). Antidepressant treatment of post-stroke depression is
warranted and, in addition to alleviating depression, may foster
recovery of cognitive function (45) and significantly increase
Depressive disorders also appear related to the occurrence of heart
attack, or myocardial infarction (MI). Persons with a history of
major depression are more than four times as likely to have an MI than those
with no history of depression (47), and high levels of
depressive symptoms are associated with an increased risk of MI
Approximately one in six persons who have experienced an MI
suffer from major depression, and at least twice that many
experience significant depressive symptoms (49). Patients who
have had an MI and are also depressed have more medical comorbidities (50) and cardiac complications (51) and are at
greater risk for mortality (52) than their nondepressed peers.
Increased mortality is also evident in persons who had an MI and
who manifest very low levels of depressive symptoms (53),
underscoring the importance of mental health to physical health
Persons with depression following an MI are less likely to
adhere to recommended lifestyle and behavioral changes,
potentially increasing their risk for subsequent cardiac events
(54). This is particularly unfortunate because cardiac
rehabilitation has been found to improve depressive symptoms
(55). However, the use of a specific class of antidepressant
medications — the selective serotonin reuptake inhibitors
(SSRIs) — may, in addition to their beneficial effect on
depression, exert antiplatelet effects protecting against MI
(56). In addition to being safer in overdose (57), SSRIs are also
less likely to induce arrhythmia than other classes of
antidepressant medications (58). It has further been concluded
that the combination of CBT with an SSRI is frequently the most
effective treatment of depression in persons with CVD (59).
Estimates of the prevalence of psychiatric disorders among
persons with cancer vary widely, depending on the type of cancer
and its clinical stage. Previous research indicates that nearly
50% of patients newly admitted to a cancer center met diagnostic
criteria for a psychiatric disorder. Adjustment disorders —
distress related to a specific precipitant — comprised 68%
of these diagnoses, although many of those diagnosed reported
anxiety or depression as a central symptom (60). Among cancer
patients judged terminally ill, 53% met psychiatric diagnostic
criteria, with delirium — a fluctuating change in cognition
and disturbance in consciousness — being the most
frequently diagnosed disorder (61).
In addition to delirium, cancer
patients also suffer from depression and anxiety (62); 21% of cancer patients
are reported to be depressed (63).
Depression assumes particular significance in the care of
individuals with cancer, because it has been associated with a
desire for hastened death among terminally ill cancer patients
(64), and increased depressive symptoms are inversely related to
survival (65). Of cancer patients in an intensive care unit who
were assessed as being at high risk for hospital death, 40%
reported depression (66), suggesting that diagnosis and treatment
of depression are inadequate. Strikingly, among cancer
patients undergoing chemotherapy and experiencing anemia-related
fatigue, improved hemoglobin levels have been reported to reduce
depressive symptoms (67), further suggesting the importance of
physical health to mental health status.
A previous survey of psychotropic prescription practices at
five major oncology centers revealed hypnotics to be the most
widely prescribed drugs, with antidepressants comprising only 1%
of psychotropic prescriptions (68). Subsequent research, however,
has indicated an increase of antidepressant use in community
cancer care, with 19.2% of breast, 11% of colon, and 13.7% of
lung cancer patients receiving antidepressants during a two-year
Despite the observation that both antidepressants and
psychotherapy are effective in treating depression in patients
with cancer, research on antidepressant pharmacotherapy and psychotherapy among persons with cancer has been
characterized as largely lacking randomized placebo-controlled
trials (70). Moreover, antidepressant prescription has been found
to be associated with factors not specifically related to
psychopathology, such as patient age or the presence of pain
(69), and some speculate that most depressed patients with cancer
do not need medication (71). This belief, however, may reflect
the misconception that depression is a “natural” response to
cancer and does not merit systematic diagnosis and treatment
Research suggests that depression in persons with cancer is
amenable to treatment. Among cancer patients with a life
expectancy of at least 12 months, CBT has been associated with
significantly decreased depressive symptoms across a four-month
interval (73). CBT has also been associated with decreased pain, reduced symptomatic distress (74), and subsequent improvement
in cellular immune function (75).
Adoption of a depression screening program and antidepressant
algorithm by oncologists resulted in significant improvements in
mood and quality of life among cancer patients (76). Similarly, a
placebo-controlled trial of antidepressant medication in advanced
cancer patients demonstrated that antidepressant therapy
decreased depressive symptoms and improved patient assessments of
quality of life (77). In addition to reducing the risk of
depression, data suggest that physical activity may also decrease
the risk of colon, breast, and lung cancer (78).
Elevated rates of depression have consistently been associated
with diabetes (79), with results of a meta-analysis indicating
depression is twice as prevalent among persons with diabetes than
it is among persons without diabetes (80). While it has been proposed that
depressive symptoms may be a risk factor for the development of
diabetes, this association is most pronounced at high levels of
depressive symptoms and, interestingly, only observed among
persons with less than a high school education (81). These
findings suggest that factors associated with low socioeconomic
status may contribute to the development of diabetes among
persons with substantial depressive symptoms.
Comorbid depressive symptoms or depression among persons with diabetes have
been associated with adaptation to the illness (82), diabetic-related
complications (79), unemployment (83), and illness intrusiveness, a construct
defined as the degree to which diabetes disrupts valued activities and interests
(84). As is true in the general population, depression was more prevalent among
women than among men with diabetes (80,85) and among younger adults (85).
Depressive symptoms are more likely to persist among persons with multiple
diabetic-related complications and those with less than a high school education
(79). In a prospective community-based study, baseline depressive symptoms were
positively associated with fasting insulin levels and physical inactivity (86).
A diagnosis of diabetes and self-reported depression were positively associated with sedentariness in both bivariate and multivariate analyses (87).
Compared with their nondepressed peers, patients with diabetes who
were diagnosed with depression were more likely to report
frequent overeating of sweets and high-fat foods and were less
satisfied with their ability to adhere to a diabetic diet away
from home (88).
Despite the availability of measures to screen for depression,
it is estimated that less than 25% of those with depression are
diagnosed and treated (89). This is particularly disconcerting
because the treatment of depression appears to be associated with
improved glycemic control (90). Furthermore, because depression is
associated with diabetic complications (91), treatment of
depression may also reduce diabetes-related disability. Compared
with their nondepressed peers, persons with diabetes and depression
have higher ambulatory-care use and fill more
prescriptions. Total health expenditures for persons with
diabetes and depression were 4.5 times higher than for those
without depression: $247 million compared with $55 million
Research has revealed that both CBT (90) and antidepressant
pharmacotherapy (92) are associated with decreased severity of
depression among persons with diabetes and with improved glycemic
control. Thus, in addition to preventing needless suffering, the
treatment of depression among persons with diabetes offers the
added promises of substantial financial savings and improved
medical care of these individuals.
Several studies have indicated an association between
psychopathology, including depressive symptoms, and high body
mass index (BMI), or obesity. The relationship between obesity
and psychopathology differs among men and women, with a BMI
≥30 among women associated with nearly a 50% increase in the
lifetime prevalence of depressive disorders compared with nonobese
women (93). In contrast, while BMI has not been found to be related to
measures of mental well-being among men, abdominal obesity or a
high waist/hip ratio has been associated with an increased
prevalence of both depressive symptoms (94) and antidepressant
medication use (95).
Although it is important to note that most overweight or obese
persons do not suffer from mood disorders (96), significant
positive associations have been reported between BMI and
depressive symptoms (97). It has been posited that a common pathophysiology may underlie both obesity and depression. The
neurotransmitters serotonin and norepinephrine are involved in
regulating both mood and body weight and, logically, in the
treatment of both depression and obesity (98). Antidepressant
medications available before the development of SSRIs frequently induced weight
gain; newer agents generally do not
stimulate appetite, thus making them potentially useful in
depressed patients who do not wish to gain weight (99).
Previous longitudinal research has examined the relationship
between depressive symptoms or psychological well-being and
weight gain. Women who were either normal weight or overweight at
baseline and who had experienced a recent weight gain scored
lower on a measure of psychological well-being than women who had
not gained weight (100). Similarly, persons who were overweight
and depressed at baseline demonstrated a significantly increased
likelihood of subsequent weight gain relative to those who were
not depressed. Among the highest quintile of baseline BMI, this
relationship was stronger among women (with an odds ratio of 2.2)
than men (with an odds ratio of 1.3) (101).
Cognitive behavioral interventions have been useful in managing obesity,
largely by modifying eating behaviors and dietary choices in addition to decreasing psychological distress
and sedentariness (102). In addition to fostering weight loss,
CBT has been found to improve self-reported mental health among
obese persons (103). However, psychosocial difficulties have been
associated with weight gain following initial weight loss among
obese individuals who had received CBT (104), with long-term CBT
compliance being particularly low among persons with binge-eating
Strikingly, children and adolescents with major depressive
disorder appear to manifest an increased risk for subsequently
becoming overweight (96), suggesting that both depressive
disorders and their treatment are relevant to the prevalence of
obesity. The relationship between obesity and depressive
disorders thus appears to be reciprocal, with advances in the
recognition and treatment of each of these diseases potentially
fostering improved mental and physical health.
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Research examining the association between depressive
disorders and chronic disease suggests that timely diagnosis and
treatment of psychiatric disorders could greatly affect the
impact of chronic disease. The presence of mental illness may be
an important contributor to the etiology of chronic disease.
Thus, the promotion of mental health would likely result in reducing a considerable proportion of
the burden of chronic disease. Similarly,
the presence of depressive disorders often adversely affects the
course and complicates the treatment of chronic disease. It is
important to remember that untreated depressive disorders
characteristically assume a chronic course (106), thereby adding
to the burden of chronic disease in their own right. Multivariate
investigation of the associations among depressive disorders,
chronic disease, and a variety of medical and sociodemographic
characteristics would provide valuable insights into contemporary
notions of health and quality of life.
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Corresponding author: Daniel P. Chapman, PhD, Emerging
Investigations and Analytic Methods Branch, Division of Adult and
Community Health, National Center for Chronic Disease Prevention
and Health Promotion, Centers for Disease Control and Prevention,
4770 Buford Highway NE, Mailstop K-45, Atlanta, GA 30341.
Telephone: 770-488-5463. E-mail: email@example.com.
Author affiliations: Geraldine S. Perry, DrPH; Tara W. Strine,
MPH, Division of Adult and Community Health, National Center for
Chronic Disease Prevention and Health Promotion, Centers for
Disease Control and Prevention, Atlanta, Ga.
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